Personalized genomic medicine: non-small-cell lung cancer and anaplastic lymphoma kinase

Abstract

Genomic medicine, that is to say, using genomic information about a patient in order to set the diagnostic path and to tailor therapy to his/her specific characteristics, is one of the cornerstones of modern precision medicine and forms an integral part of several fields, oncology first of all. Lung cancer is the leading cause of cancer mortality, causing more than 1.6 million deaths worldwide per year and non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancers. In a small subset of NSCLC (5%-8%), we can detect a genomic rearrangement on chromosome 2, between the Echinoderm microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphoma kinase (ALK) gene, resulting in the chimeric protein EML4-ALK, that acts as an oncogene and that can be specifically targeted by an ALK-tyrosine kinase inhibitor (TKI) therapy. However, a major clinical challenge is represented by the fact that, after a first line ALK-TKI treatment, patients eventually develop acquired resistance to these agents, opening new scenarios for the right second-line drug choice.

Keywords

Precision medicine / genomic medicine / non-small-cell lung cancer / Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase / anaplastic lymphoma kinase / tyrosine kinase inhibitor

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